PMID- 22412373
OWN - NLM
STAT- MEDLINE
DCOM- 20120709
LR  - 20211021
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 8
IP  - 3
DP  - 2012
TI  - Significant association of KIR2DL3-HLA-C1 combination with cerebral malaria and 
      implications for co-evolution of KIR and HLA.
PG  - e1002565
LID - 10.1371/journal.ppat.1002565 [doi]
LID - e1002565
AB  - Cerebral malaria is a major, life-threatening complication of Plasmodium 
      falciparum malaria, and has very high mortality rate. In murine malaria models, 
      natural killer (NK) cell responses have been shown to play a crucial role in the 
      pathogenesis of cerebral malaria. To investigate the role of NK cells in the 
      developmental process of human cerebral malaria, we conducted a case-control 
      study examining genotypes for killer immunoglobulin-like receptors (KIR) and 
      their human leukocyte antigen (HLA) class I ligands in 477 malaria patients. We 
      found that the combination of KIR2DL3 and its cognate HLA-C1 ligand was 
      significantly associated with the development of cerebral malaria when compared 
      with non-cerebral malaria (odds ratio 3.14, 95% confidence interval 1.52-6.48, 
      P = 0.00079, corrected P = 0.02). In contrast, no other KIR-HLA pairs showed a 
      significant association with cerebral malaria, suggesting that the NK cell 
      repertoire shaped by the KIR2DL3-HLA-C1 interaction shows certain functional 
      responses that facilitate development of cerebral malaria. Furthermore, the 
      frequency of the KIR2DL3-HLA-C1 combination was found to be significantly lower 
      in malaria high-endemic populations. These results suggest that natural selection 
      has reduced the frequency of the KIR2DL3-HLA-C1 combination in malaria 
      high-endemic populations because of the propensity of interaction between KIR2DL3 
      and C1 to favor development of cerebral malaria. Our findings provide one 
      possible explanation for KIR-HLA co-evolution driven by a microbial pathogen, and 
      its effect on the global distribution of malaria, KIR and HLA.
FAU - Hirayasu, Kouyuki
AU  - Hirayasu K
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Bunkyo-ku, Tokyo, Japan. hirayasu@ifrec.osaka-u.ac.jp
FAU - Ohashi, Jun
AU  - Ohashi J
FAU - Kashiwase, Koichi
AU  - Kashiwase K
FAU - Hananantachai, Hathairad
AU  - Hananantachai H
FAU - Naka, Izumi
AU  - Naka I
FAU - Ogawa, Atsuko
AU  - Ogawa A
FAU - Takanashi, Minoko
AU  - Takanashi M
FAU - Satake, Masahiro
AU  - Satake M
FAU - Nakajima, Kazunori
AU  - Nakajima K
FAU - Parham, Peter
AU  - Parham P
FAU - Arase, Hisashi
AU  - Arase H
FAU - Tokunaga, Katsushi
AU  - Tokunaga K
FAU - Patarapotikul, Jintana
AU  - Patarapotikul J
FAU - Yabe, Toshio
AU  - Yabe T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120308
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Epitopes)
RN  - 0 (HLA-C Antigens)
RN  - 0 (KIR2DL3 protein, human)
RN  - 0 (Ligands)
RN  - 0 (Receptors, KIR)
RN  - 0 (Receptors, KIR2DL3)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Case-Control Studies
MH  - Endemic Diseases
MH  - Epitopes
MH  - Evolution, Molecular
MH  - Gene Expression Regulation
MH  - *Genetic Predisposition to Disease
MH  - Genetic Variation
MH  - Genotype
MH  - HLA-C Antigens/*genetics
MH  - Humans
MH  - Killer Cells, Natural/immunology
MH  - Ligands
MH  - Malaria, Cerebral/*genetics/immunology
MH  - Parasite Load
MH  - Receptors, KIR/*genetics
MH  - Receptors, KIR2DL3/*genetics
MH  - Selection, Genetic
MH  - Young Adult
PMC - PMC3297587
COIS- The authors have declared that no competing interests exist.
EDAT- 2012/03/14 06:00
MHDA- 2012/07/10 06:00
PMCR- 2012/03/08
CRDT- 2012/03/14 06:00
PHST- 2011/08/06 00:00 [received]
PHST- 2012/01/19 00:00 [accepted]
PHST- 2012/03/14 06:00 [entrez]
PHST- 2012/03/14 06:00 [pubmed]
PHST- 2012/07/10 06:00 [medline]
PHST- 2012/03/08 00:00 [pmc-release]
AID - PPATHOGENS-D-11-01763 [pii]
AID - 10.1371/journal.ppat.1002565 [doi]
PST - ppublish
SO  - PLoS Pathog. 2012;8(3):e1002565. doi: 10.1371/journal.ppat.1002565. Epub 2012 Mar 
      8.